The diagnosis of SPCC generally requires the demonstration of both malignant spindle cells and squamous cell carcinoma, either in-situ or invasive. When a SCC component is inconspicuous, then the spindle cells should be investigated for evidence of epithelial differentiation. However, even in the absence of SCC and negative epithelial markers, SPCC cannot be entirely ruled out. In the larynx and hypopharynx sarcomas are very rare, and SPCC is still more likely. SPCC can also be confused with reactive or benign spindle cell proliferations, such as nodular fasciitis, and inflammatory myofibroblastic sarcoma, and low-grade myofibroblastic sarcoma, and myoepithelial carcinoma.
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